Understanding the biological events in pemphigus antibody induced cell dyshesion has broad biological significance. We have shown that pemphigus IgG induces proteinase activation in mouse and human epidermal cells. This proteinase degrades casein and Iodinated epidermal cell surface proteins. Action of this enzyme upon epidermal cells may be responsible for the acantholysis characteristic of pemphigus. Incubation of anti-cell surface melanoma antibody with melanoma cells in culture also induces proteinase activation. We will isolate, purify and characterize the proteinase induced by incubating epidermal cells with pemphigus antibody. We also expect to produce a monoclonal antibody to this enzyme. We will determine the nature of the epidermal cell surface proteins cleaved by the enzyme and determine which of these proteins is important in epidermal adhesion. We will explore the specificty of proeinase activation in different cell types, (human epidermis, human fibroblast, human melanoma, mouse epidermis) and define variations between cells in attachment proteins. We will study the molecular events involved in proteinase activation. We will also explore the use of phorbol esters as a model for pemphigus induced proteinase activation. Finally we are trying to develop in vitro models for synthesis of pemphigus IgG.